We have been studying the biosynthesis of the antibiotic streptothricin F for the past two years. Making use of stable isotopes and NMR techniques, we have obtained evidence for the identity of the primary precursors and of the interaction of primary metabolic grids with the secondary pathways leading to the antibiotic. We intend to continue our streptothricin work, focusing on stereochemical aspects of the biosynthesis and expanding the scope to include the transformations from glucose to the aminoglycoside moiety. We will begin work on three additional antibiotics that we believe to be biogenetically related to streptothricin: blasticidin S, negamycin, and 3-epideoxynegamycin. Again, we will primarily use stable isotope techniques and focus on sugar transformations and stereochemical consequences of each pathway. Our investigations will increase our understanding of which chemical reactions are available in Nature and how they can be linked to produce complex structures. They may also provide the opportunity to produce new analogs, also with antibiotic activity, by redirecting the microorganisms' biosynthetic apparatus to use modified precursors.